Swine have a long history of use in the biomedical community as outstanding models for translational research. With the development of somatic cell nuclear transfer (SCNT), and the completed sequencing of the porcine genome it is now possible to generate, and carefully analyze, a wide range of genetically modified porcine models of human disease. These includes existing porcine models of cystic fibrosis, skin cancer, diabetes, retinitis pigmentosa, macular degeneration, and a wide range of pigs for xenotransplantation. This is in addition to the large number of models that are being generated at present. The value of swine in biomedical research, has been recognized by the NCRR/NIH with the creation of the National Swine Resource & Research Center (NSRRC). Thus, this is a valuable and emerging field in biomedical research that will have significant impact in basic and translational advances. Unfortunately, the great majority of these valuable transgenic lines are developed using commercial swine breeds. As a result, the animals grow to sizes that can reach >500 lb. This makes housing and management difficult, as most biomedical research centers do not have adequate facilities that can handle large swine. Therefore, in order the maximize the use of these valuable lines it would be greatly advantageous if a system was available to easily reduce the size of existing large transgenic lines in a single breeding. This could be accomplished by mating the line of interest with a transgenic animal carrying a transgene that induces dwarfism in a dominant manner (does not have to be bred to homozygocity) without any other deleterious effects that would affect the phenotype being studied. We propose the development and characterization of a transgenic pig that can be used to significantly reduce the size, and increase the usefulness, of existing swine biomedical models. Successful completion of this project will affect multiple NIH institutes as it could be applied to essentiall all existing porcine biomedical models. PUBLIC HEALTH RELEVANCE: The pig has a long history of use in biomedical research due to its physiological similarities to humans. Recently, advances in somatic cell nuclear transfer have created unique opportunities to develop genetically modified swine of great value in translational research. Unfortunately, due to their large size their broad utilization has been drastically limited. Our proposal would solve this issue and would result in a much broader utilization of these valuable animal models. This will have a positive impact in human health by accelerating the pace of discoveries based on these unique models.